SYNTHESIS : To a cooled and well-stirred solution of 16 g
5-methoxyindole in 200 mL anhydrous Et2O there was added, dropwise, 25
g oxalyl chloride. Stirring was continued for an additional 10 min,
then the red solids were removed by filtration, washed lightly with
Et2O, and returned to the reaction beaker as a suspension in 200 mL
fresh anhydrous Et2O. To this there was added a solution of 8.5 g
dimethylamine in 25 mL anhydrous Et2O which discharged the red
color. Stirring was continued for an additional 0.5 h, and the solids
were removed by filtration and washed with Et2O. These were suspended
in H2O, filtered, and washed alternately with H2O and
Et2O. Recrystallization from THF / Et2O provided 20 g (75%)
5-methoxy-N,N-dimethylindol-3-ylglyoxylamide, mp 223-223.5 °C, as
fine white crystals.

To a well-stirred suspension of 11.7 g LAH in 350 mL anhydrous Et2O
there was added, in small portions, a suspension of 18.5 g
5-methoxy-N,N-dimethylindol-3-ylglyoxylamide in 200 mL hot
benzene. The last of the solids were rinsed in with anhydrous Et2O and
the mixture held at reflux for 1.5 h. After cooling with an external
ice bath, the reaction complex and excess hydride were decomposed by
the cautious addition of H2O. The inorganic solids were removed by
filtration, the filter cake washed with additional Et2O, the filtrate
and washing were combined and dried over anhydrous MgSO4, and the
solvents removed under vacuum. The residue was distilled at the
KugelRohr to provide a colorless fraction distilling at 160-170 °C
at 0.6 mm/Hg, that crystallized on cooling. There was thus obtained
12.8 g (78%) 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) which on
recrystallization from hexane had a mp 69-70 °C. The hydrochloride
salt can be made by passing a stream of hydrogen chloride gas through
an Et2O solution of the base. It, upon recrystallization from EtOH /
Et2O, had a mp of 145-146 °C.

DOSAGE : 6 - 20 mg, smoked; 2 - 3 mg, i.v.

DURATION : 1 - 2 hrs

QUALITATIVE COMMENTS : (with 6 mg, smoked) "I felt it in a
minute -- not really light head, but the head feels close to the lower
parts of the body -- close to the ground -- knees weak -- distinct
shakes. I peaked at 2 or three minutes. It was quite intense, but not
the max of DMT at 30 milligrams and no sensory close-out. Slight
nausea on the drop-off -- I am glad I had not eaten anything. Overall
comparison to DMT, more potent, slightly faster, but like DMT is
largely a simple, stoning drug with no sensory contribution, no
intellectual contribution. It's greatest contribution might be to
provide a subject the vocabulary of an altered state of consciousness
so that, with interesting and constructive drugs, these effects will
be familiar, and thus not distractions."

(with 8 mg, smoked) "I was blown away, far away I might add, but only
for 10 minutes and effects were gone by half an hour. During this
episode mental activity was almost absent. I can't say I wasn't
'impressed' in some way, though it wasn't exactly what I expected. I
had read reports with statements varying from 'dwarfs + elves' to
'conk on the head,' the latter of which relates more closely to my
experience."

(with perhaps 10 mg, smoked) "Onset was gentle, perhaps over 15
minutes. I felt like all of my blood had turned to concrete. There
were no noticeable visual effects, but my hearing was slightly
diminished. The whole experience was over after 1 hour."

(with perhaps 15 mg, smoked) "I took a hit from the pipe with
five-methoxy in it, and after the 8 to 10 seconds it took to carry the
chemical to my brain I remember starting to fall over from my sitting
position. My normal physical perceptions dissolved away from my
awareness. My ears started to ring and I started to float off. I was
acutely aware of a certain resonation of my aural perception, an
electrical buzzing that fluctuated in synch with my visual
perception. What I saw can only be described as a fantastically subtle
multicolored phosphene, completely filling every area visually
available. I say it in this way because I was simultaneously losing
contact with my body, I could not tell if my eyes were open or shut,
although I initially had the feeling that they were darting back and
forth, from side to side. These feelings and sensations built up in
intensity very quickly, a matter of seconds: I can remember this
feeling of building intensity up to a point, and then I was not there
in my body or in time. In the 10 to 15 minutes that my body was under
the influence of the drug my mind was completely referenceless, there
was no way for my consciousness to limit or gauge the stimuli my being
was barraged with. I remember switching to a perception where the
endless and intricate phosphene was love and the energy of light. I
called upon those forces within my being to realign and submit, to let
go of all the cogent fears and just exist ... and that innate decision
saved me a lot of psychic damage. What is most outstanding about the
way it feels is an inability to judge in any way, by any method of the
mind ... it is unconquerable, as deep and profound as a totally
unconditional love that is life. What a trip, huh?"

(with 15 mg, smoked) "At about 60 seconds after I smoked this free
base, I beheld every thought that was going on everywhere in the
universe and all possible realities while I was wracked out with this
horrible ruthless love. It scared the hell out of me. When I could see
again (15 minutes later) it was almost as if there was an echo of a
thought in my head saying that I was given an extremely rare look at
the true consciousness of it all. I've never been hit this hard since
then. A definite ++++."

(with perhaps 20 mg, smoked) "This is a very strong hallucinogen. A
twenty minute experience. For me it was like adding the MDMA
experience to DMT. DMT for me is terrifying (I still go back though)
and I must really think about it before proceeding. The 5-MeO-DMT was
much more relaxed, a kind of cosmic consciousness type of
experience. I broke into a space similar to DMT but it was more like
receiving grace. I felt a little shaky (tremor-like) coming down."

(with 25 mg, smoked) "I placed 25 mg of 5-methoxy-DMT in a stainless
steel one-quarter teaspoon and vaporized it over a cigarette lighter
collecting the smoke in an upside-down funnel. All smoke was inhaled;
the taste was mild -- none of the plastic taste of DMT. About 10
seconds or so after inhaling the last of the smoke, it began with a
fast-rising sense of excitement and wonder, with an undertone of "Now
you've done it," but dominated by a sense of, "WOW, This Is IT!" There
was a tremendous sense of speed and acceleration In perhaps 10 more
seconds these feelings built to an intensity I had never experienced
before. The entire universe imploded through my consciousness. It's as
if the mind is capable of experiencing a very large number of objects,
situations and feelings, but normally perceives them only one at a
time. I felt that my mind was perceiving them all at once. There was
no distance, no possibility of examining the experience. This was
simply the most intense experience possible; a singularity, a
white-out (as opposed to a black out), I have little memory of the
state itself. I have no memory, for example, of whether my eyes were
opened or closed. After some seconds or minutes , it started to fade
and came to resemble a merely intense psychedelic state. Here I had
the feeling, a visualization of being part of the universe of beings,
all active in our daily, interwoven tasks, still moving at an
incredible rate, and with a longing for a single group / organism
awareness and transcendence. In a few more minutes it faded to an
alert (+ one) state with an additional sense of awe and wonder,
relief, and a strong feeling of gratitude toward the universe in
general, for the experience."

(with 30 mg, smoking) "I placed approx. 30 mg of 5-MeO into a pipe,
and smoked it, in one toke, without a second thought. An instant
later, I was crawled up on my bed (in the fetal position) with my eyes
closed, squirming around, screaming (in my head) 'Fuck! You killed
yourself!' I repeated this several times, very fearful of death. I
didn't see anything, while my eyes were shut, except for a bright
white light, that which you see after staring at a bright light. The
only other "vision" was one in my mind - I came to the realization
that my life would be wasted if I died there. This showed me all of my
scripts being discarded and nothing good happening ever again. It was
a glimpse into my future, if I died. I concentrated on breathing and
that helped me survive (mentally). I walked into the living room and
placed a CD into the stereo, and as the first song started, my
attention span disappeared, and I walked back into my bedroom. To my
surprise, forty minutes had passed, in what I remembered as mere
seconds. This scared me, thinking that maybe I had blacked out. I felt
the effect for about an hour, it slowly faded away."

(with an unknown but large amount, smoked) I observed the subject pass
very quickly into an almost coma-like state. Within seconds his face
became purple and his breathing stopped. I pounded his chest, and
breathed for him, and he seemed to emerge in consciousness, with the
comment, "This is absolute ecstasy." He stopped breathing a second
time, and both heart massage and mouth-to-mouth resuscitation was
provided. Again, he recovered and managed to maintain a continuing
consciousness and achieve a partial recovery. In the awake condition
he was increasingly lucid, but on closing his eyes he became possessed
with, what he called, "The energy of terror." He could not sleep, as
upon closing his eyes he felt threatened in a way he could not
tolerate. Three days later, medical intervention with antipsychotic
medication was provided, which allowed the recovery of an acceptable
behavior pattern in a few more days.

(with 35 mg, orally): "No activity."

(with 0.25 mg, i.v.): "A real effect."

(with 0.5 mg, i.v.) "I felt the effects distinctly within a minute,
along with some pain at the injection site. In a few minutes I felt a
very distinct calming and stilling of my mind. While I could have
carried on a conversation about anything and didn't feel the least bit
stoned, I found the feeling very recognizable."

(with 0.7 mg, i.v.): "This was basically a +1 experience. After a few
instances I felt its motion, very gentle waves. I was thinking about
thinking about the experience, about writing about it, and so I was
experiencing myself as both observer and editor. This was not
overwhelming, but gentle."

(with 1.3 mg, i.v.) "In a few seconds I was participating in
exquisite, full body, teeth-chattering shivers that lasted in all
about 10 minutes, nearly the duration of the effects. The sensations
seemed to come more from my head region, whereas my 'full blown'
experiences of smoked 5-MeO-DMT seemed to emanate from my center and
heart."

(with 2.3 mg, i.v.) "I remember having a perspective of knowing I was
aware and, if not from the start of the experience then very soon into
it, knowing I knew I was aware. I thought I was an ocean. I don't
remember where I first lost continuity of consciousness (this is a
little like a black-out from hard liquor) but I remember being aware
of the sounds I was making apparently some time after I began
vocalizing. Around the time I thought to change these sounds as I
pleased, I also noted with brief wonder that the sound was continuous,
not changed by my breathing. I sang my way back."

(with 3.1 mg, i.v.) "I vocalized effortlessly. I was getting in touch
with my body. I said, 'Turn off the lights,' and 'I love you,' and
then I lost it. I was amazed later to find a roomful of people who had
been frightened by the noises they had been amazed to hear, and I was
amazed to be told I had made."

EXTENSIONS AND COMMENTARY : This is, like DMT, another
naturally occurring alkaloid that is not orally active. And, as with
DMT, it is almost always smoked. This is the reason that both there
and here, there are several entries with the word "perhaps" in the
dosage statement. When the transportation vehicle is a rolled joint
containing some inert plant carrier, or a glass pipe heated with a
torch, who can accurately say how much of the drug was actually
volatilized and drawn into the lungs? Further, from the qualitative
range of responses, one can truly say, it is different things to
different folks. I don't know of any active oral level (I have been
told of it being tried at 35 milligrams) but a number of experiments
with oral 5-MeO-DMT preceded by harmaline have shown activity in the
10 - 25 milligram area. These are discussed in the Hoasca
vs. Ayahuasca chapter. Some trial i.v. experiments with radioactively
labeled and unlabeled materials showed no effects at 100 micrograms,
but real effects at 250 micrograms. Higher levels have convincingly
established the enhanced potency that is the result of this route. The
injection process is faster than the smoking process, and it avoids
the smoke's odd flavor.

5-MeO-DMT was first observed in a member of the Rue family (Rutaceae)
called Dictyoloma incanescens. Now it is recognized as a major
component of a number of South American snuffs. The snuff called
cohoba is generally associated with plants of the Piptadenia and
Mimosa genus, and as they are largely DMT-containing, they are
discussed under that entry. But there are other snuffs, such as yakee
and yato (in Colombia) and paricá, epená and nyakwana in Brazil,
which should probably be discussed here. The plants used are of the
Virola genus, containing trees most plentifully found in the Amazon
basin.

There has been a long-standing and never-to-be-resolved disagreement
amongst botanists as to the best way of classifying plants. There are
the morphotaxonomists, who insist that species assignment should be
based primarily on appearance, and there are the chemotaxonomists who
feel that the natural composition should be a deciding factor in the
distinction between species. But the ultimate requirement for
morphology is to find the plant in bloom, and for chemistry, to have
some analytical capabilities. Often, neither luxury is available in
the jungles of the rain forest. A major contributor to the Virola
snuffs, Virola theiodora, is a good case in point. Two plant sources,
both gathered in Brazil, have been found to have radically different
compositions. In one, 5-MeO-DMT is substantially the only alkaloid
found in the bark, whereas in the other, DMT is the major
alkaloid. But both have DMT almost exclusively in the young green
shoots. Are they the same species? Another plant used in some of the
snuff preparations is Virola calophylla, where the bark, root, leaves
and shoots all run about 90% DMT as the alkaloid content. Yet, the
alkaloids in the root and bark of Virola rufuta consist of some 95%
5-MeO-DMT.

The inquiries into metabolic 6-hydroxylation as a prelude to
biological activity have been made with both 5-MeO-DMT and the
corresponding primary tryptamine (see below). 6-HO-5-MeO-DMT has been
shown in several animal models to be pharmacologically less active
than its parent compound. See the discussion under DET for the role
that this metabolism played in some early clinical studies.

Removing one of the N-methyl groups provides
N-methyl-5-methoxytryptamine (5-MeO-NMT), which has its own
entry. Removal of both methyl groups from the nitrogen gives
5-methoxytryptamine (5-MeO-T) which has been explored most extensively
by Soviet researchers as a treatment for exposure to radiation; this
aspect of its action is discussed and expanded upon in the commentary
under Melatonin. It is also known by the trade name Mexamine and has
been looked at as a potentiator of centrally active drugs. Here, as
with the simpler N,N-dialkyltryptamines, the metabolic introduction of
a hydroxyl group at the 6-position (to give 6-HO-5-MeO-T) leads to a
lowering of pharmacological potency. And again, no human studies have
been reported.

A true academic challenge exists with the many studies of
5-methoxy-DMT (as has been mentioned under DMT, different drug, same
problem) which have involved drug mixtures. The second drug, added to
the tryptamine, is almost always a monoamineoxidase inhibitor such as
harmaline, either as a chemical (in most clinical studies in the
Northern Hemisphere) or as the plant decoction (in most jungle uses in
the Southern Hemisphere). The challenge is, just how should one
classify these observations? Under the first drug modifying or being
modified by the second? Under the second drug modifying or being
modified by the first? Or should the mixture be treated as a variable
thing in its own right?

Since the mixture invariably shows properties that neither component
can show alone, it is obvious that the combination is a major
classification component. When the harmaline component is a plant
mixture containing harmaline, a common name that is used is
Ayahuasca. This can be any of a large number of carboline-containing
plants (or even harmaline itself) combined with a really wide variety
of amines ranging from the tryptamines to mushrooms to such diverse
materials as Jimpson Weed components. These combinations are usually
unknown as to exact composition, and they will be discussed in a
chapter devoted to just this combination, entitled "Hoasca
vs. Ayahuasca." On the other hand, when the components are discrete
compounds, the process is much more controlled (in the experimental
sense rather than in the effects sense) and these combinations are
gathered in the recipe for harmaline.

There are a couple more entries for 5-MeO-DMT, one very important one,
and the other quite trivial. There is a drug-use phenomenon that is
often referred to by the popular title of "toad-licking." The toad
involved is the Sonora Desert Toad, also called the Colorado River
Toad, and carries the binomial Bufo alverius. It is not the closely
related marine toad Bufo marinus, as some people have insisted,
prompted by the early Olmec and Mayan iconography. Of course the
licking myth is newspaper hype -- it is the venom that is active, and
it is smoked. When the desert toad is stroked near the parotid glands
in the neck region, there is the squirting out of this venom and when
it is allowed to dry on a hard surface it takes on the texture of
rubber cement. It contains up to 15% 5-MeO-DMT, as well as
N-methyl-5-methoxytryptamine, 5-MeO-NMT and Bufotenine, which have
their own entries.

And here is the trivial entry. I involved myself in a small Australia
/ toad incident when I recently visited Sydney. There is a consistent
historical record of the axiom "the road to Hell is paved with good
intentions" in the effort to import solutions to problems that were
the unforeseen consequences of earlier imported solutions. I can't
remember the decade-by-decade record but as I remember it involved,
amongst other things, dogs, rabbits, viruses to control rabbits, and
maybe mongooses. And cattle. Cattle had been imported in mid-century
as a desired agricultural commodity, but it could not be predicted
that their cow-plops would not deteriorate. There were domestic dung
beetles, but they appreciated kangaroo droppings (raisin-sized) rather
than cow-plops (birthday-cake sized). So the eggs of a cow-oriented
dung beetle were brought in about 1970 and, after weathering the usual
quarantine, were released into the ecosphere. Another beetle came in
without invitation with the importation of agricultural
cane. Hitch-hiking along with the cane was a cane beetle, and it had
no natural enemies. The beetle proliferated, and as a solution to this
infestation there was brought in a "cane toad," the Bufo marinus (the
marine toad, not the desert toad, to the eventual disappointment of
the drug-oriented subculture) which was believed could provide some
control over them. Well, it turned out that the beetles lived at the
top of the cane stalks, and the frogs lived at the bottom. The toad
didn't eat the beetles, but they did successfully reproduce and
multiply, because they, too, had no natural enemies. They are today
sweeping across north-eastern Australia.

In the middle of downtown Sydney, right alongside Hyde Park at
Williams and College, there is the Australian Museum, with a super
library of natural history which I wished to use in the pursuit of the
Aborigine use of red beans. And there was a special exhibit on display
of the frogs and toads of Australia, with histories, photographs, and
occasional sound tracks of croakings. I spotted a panel devoted to the
origins and short history of the Bufo marinus. And right in front of
it was a little old lady diligently reading the text which said,
approximately, that a virus was being developed at some research
laboratory in South America, that would be specific for this toad and
which would bring the problem under control. I wondered to myself, but
just loud enough for her to hear, if this was the same virus that
could cause the AIDS syndrome in the Wallaby?

She looked at me for a moment, turned, and walked away. Maybe, just
maybe, another rumor of unknown origin has been launched.